This Mouse-BIRN renewal application describes a research and development effort that will result in a distributed adaptive database and multiscale, multimodality atlases of the mouse brain. Tools to incorporate and compare data from gene expression patterns to gross morphology from multiple laboratories at scales from nanometers to centimeters will be built. The goals are to create an infrastructure for relating previously disparate data collections into a single system capable of quantitative visualization and linkage with previously disconnected knowledge bases. Mouse-BIRN will integrate the activities of five laboratories - the Laboratory of Neuro Imaging (LONI) at UCLA, the Biological Imaging Center (BIC) at CalTech, the Center for In Vivo Microscopy (CIVM) at Duke University, the Mouse Brain Library (MBL) at UT and the National Center for Microscopy and Imaging Research (NCMIR) at UCSD. The Mouse-BIRN is structured as five Cores titled: Imaging, Atlasing, Data Federation, Applications, and Administration. The Imaging Core will acquire data for the entire project, encompassing imaging modalities from the whole brain scale to the supramolecular. The Atlasing Core will enable the processing of imaging data, reconstruction and registration of it, using techniques to integrate the various data collected into multimodal digital atlases. The Data Federation Core will organize, manage, and archive all the data collected and develop mechanisms for interaction between databases. The Applications Core contains the neurodegenerative disease test beds, the research projects that drive the development of infrastructure. And finally, the Administration Core will manage communication between and within Cores, to the BIRN Central Coordinating site (BIRN-CC), and to the scientific community at large. The infrastructure will be examined by focusing the neuroscience of this project on degenerative brain disease. We chose this for several reasons. First, there are degenerative diseases such as Alzheimer's disease (AD), multiple sclerosis (MS), and Parkinson's disease (PD) that result in characteristic morphological changes that can be detected in vivo and histologically. There are effects in gray and white matter that can be measured, catalogued, and visualized. Second, these diseases have mouse models that could greatly benefit from the integrative approach proposed here. Third, AD is the focus of MorphBIRN and a synergy afforded by comparisons between these two BIRN efforts will be amplified with a common disease test bed. The Experimental Autoimmune Encephalomyelitis (EAE) model of MS and the alpha-synuclein knock-out model of PD examined during the previous funding cycle demonstrated the feasibility and potential of this model to utilize the tools and infrastructure proposed here.